The Urine Proteome Profile Is Different in Neuromyelitis Optica Compared to Multiple Sclerosis: A Clinical Proteome Study

PLoS One. 2015 Oct 13;10(10):e0139659. doi: 10.1371/journal.pone.0139659. eCollection 2015.

Abstract

Objectives: Inflammatory demyelinating diseases of the CNS comprise a broad spectrum of diseases like neuromyelitis optica (NMO), NMO spectrum disorders (NMO-SD) and multiple sclerosis (MS). Despite clear classification criteria, differentiation can be difficult. We hypothesized that the urine proteome may differentiate NMO from MS.

Methods: The proteins in urine samples from anti-aquaporin 4 (AQP4) seropositive NMO/NMO-SD patients (n = 32), patients with MS (n = 46) and healthy subjects (HS, n = 31) were examined by quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) after trypsin digestion and iTRAQ labelling. Immunoglobulins (Ig) in the urine were validated by nephelometry in an independent cohort (n = 9-10 pr. groups).

Results: The analysis identified a total of 1112 different proteins of which 333 were shared by all 109 subjects. Cluster analysis revealed differences in the urine proteome of NMO/NMO-SD compared to HS and MS. Principal component analysis also suggested that the NMO/NMO-SD proteome profile was useful for classification. Multivariate regression analysis revealed a 3-protein profile for the NMO/NMO-SD versus HS discrimination, a 6-protein profile for NMO/NMO-SD versus MS discrimination and an 11-protein profile for MS versus HS discrimination. All protein panels yielded highly significant ROC curves (AUC in all cases >0.85, p≤0.0002). Nephelometry confirmed the presence of increased Ig-light chains in the urine of patients with NMO/NMO-SD.

Conclusion: The urine proteome profile of patients with NMO/NMO-SD is different from MS and HS. This may reflect differences in the pathogenesis of NMO/NMO-SD versus MS and suggests that urine may be a potential source of biomarkers differentiating NMO/NMO-SD from MS.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Cluster Analysis
  • Demography
  • False Positive Reactions
  • Female
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Multiple Sclerosis / urine*
  • Neuromyelitis Optica / urine*
  • Principal Component Analysis
  • Proteome / metabolism*
  • Proteomics / methods*
  • Risk Factors
  • Young Adult

Substances

  • Proteome

Grants and funding

This work was supported financially by the Danish Society for Multiple Sclerosis (Scleroseforeningen), Region of Southern Denmark Research Grant, Odense University Hospital Research Grant, Lundbeckfonden, The Foundation for the Advancement of Medical Science, Brogaards Memorial Grant and Dir. Leo Nielsens Foundation. The funders had no role in the study design, data collection, analysis, decision to publish or preparation of the manuscript.